Prostate cancer has a complex pathogenesis in which many men develop early stage 'benign' cancers, and a much smaller but substantial number develop aggressive cancers that metastasize and cause premature death. The PI has identified a region on chromosome 13q21 which appears to contain a gene whose alteration contributes to the aggressive behavior of prostate cancer. This region is subject to LOH and homozygous deletion in aggressive prostate cancers and cell lines. The current minimal region contains at least three genes which are expressed in normal prostate and low-grade tumors, but not aggressive cancers. The PI now proposes to define the smallest region of deletions that contains the 13q21 gene; to identify the 13q21 tumor suppressor gene (TSG) through expression and mutation analyses; to express the gene in cancer cell lines to examine effects on growth and metastasis; and examine in greater detail how often LOH and homozygous deletion affect the gene, the expression of the gene in prostate cancer, and clinical and pathologic correlations including prognostic significance.